Motor Function Research Articles

Surgicogenomics: The Role of Genetics in Deep Brain Stimulation in Parkinson's Disease Patients.

Parkinson's disease (PD) is the second-most common neurodegenerative disease, affecting 1% of people aged over 60. Currently, there is only symptomatic relief for PD patients, with levodopa being the gold standard of PD treatment. Deep brain stimulation (DBS) is a surgical option to treat PD patients. DBS improves motor functions and may also allow a significant reduction in dopaminergic medication. Important parameters for DBS outcomes are the disease duration, the age of disease onset, responsiveness to levodopa and cognitive or psychiatric comorbidities. Emerging data also highlight the need to carefully consider the genetic background in the preoperative assessment of PD patients who are candidates for DBS, as genetic factors may affect the effectiveness of DBS in these patients. This review article discusses the role of genetics in DBS for PD patients, in an attempt to better understand inter-individual variability in DBS response, control of motor PD symptoms and appearance of non-motor symptoms, especially cognitive decline.

Unraveling the mysteries of parsonage turner syndrome: A journey towards optimal management. A systematic review

AimsParsonage Turner Syndrome (PTS) is a peripheral neuropathy manifesting as sudden onset pain, muscle weakness, and atrophy. This review aims to analyse long-term outcomes reported in adult patients with PTS, and establish an optimised management approach. MethodsA comprehensive literature search was performed using MEDLINE, PubMed, and the Cochrane Library. Articles that met the eligibility criteria were included. Analysis on time to presentation, presentation, interventions and long-term functional outcomes was conducted. All relevant information was collected by two independent reviewers. ResultsTwenty-five studies, comprising 950 PTS patients, were identified. Patients averaged 43.8 years in age, with a F:M ratio of 0.6:1, and presented symptoms spanning 1–24 months prior to seeking medical attention. Management details were elucidated for 402 patients (42 ​%), with 87 ​% managed conservatively. Among conservatively managed patients, over 50 ​% exhibited no improvement. 62/402 (15 ​%) necessitated surgical interventions, including neurolysis, decompression, nerve transfers, and diaphragmatic plication. 25/31 (80.6 ​%) neurolysis cases demonstrated full functional recovery, including pain resolution and full muscle strength, between 1 day and 13 months (average 2.9 months). 2 nerve transfer cases achieved full forward flexion at 2.5 months. Overall, long-term outcomes of PTS, reported at 5–25 months, revealed residual neuropathic pain in 60 ​% and incomplete motor function return in 70 ​% of patients. ConclusionsPTS recognition and referral challenges persist, impeding timely management. While surgical interventions are advocated after three months for incomplete recovery, long-term surgical outcomes are inadequately reported. An optimal surgical strategy for stagnant nerve recovery needs to be devised for this challenging cohort of patients.

Jaw-neck motor function 2 years after whiplash trauma.

There is limited knowledge about the possible long-term effects on jaw motor function after whiplash trauma. The primary aim was to evaluate integrated jaw and head-neck movement amplitudes during jaw function in individuals 2 years after whiplash trauma, compared to controls. The secondary aim was to evaluate changes between the acute stage and a 2-year follow-up in terms of jaw and head-neck movement amplitudes during jaw function. This study included 28 cases exposed to a whiplash trauma 2 years earlier (13 women) and 28 controls (13 women) without previous neck trauma. Head and jaw movement amplitudes were recorded during maximal jaw opening-closing movements using an optoelectronic 3D recording system. For a subpopulation of 12 cases and 15 controls, recordings had also been performed in the acute stage after the whiplash trauma. Jaw and head movement amplitudes were analysed using linear regression with group and sex as independent variables. The subpopulation longitudinal analysis was adjusted for movement amplitudes at baseline. Jaw movement amplitudes were significantly associated with group (coefficient: -0.359: 95% CI: -10.70 to -1.93, p = .006) with smaller amplitudes of jaw movements for whiplash cases. Head movement amplitudes were not associated with group (coefficient: -0.051, 95% CI: -4.81 to 3.20, p = .687). In the longitudinal analysis, both jaw and head movement amplitudes showed significant associations between baseline and the 2-year follow-up. The present findings indicate that the effects on jaw function in terms of jaw opening capacity in the acute stage after whiplash trauma do not spontaneously recover.

Pharmacologic activation of activating transcription factor 6 contributes to neuronal survival after spinal cord injury in mice.

The impact of primary and secondary injuries of spinal cord injury (SCI) results in the demise of numerous neurons, and there is still no efficacious pharmacological intervention for it. Recently, studies have shown that endoplasmic reticulum stress (ERS) plays a pivotal role in recovery of neurological function after spinal cord injury. As a process to cope with intracellular accumulation of misfolded and unfolded proteins which triggers ERS, the unfolded protein response (UPR) plays an important role in maintaining protein homeostasis. And, a recently disclosed small molecule AA147, which selectively activates activating transcription factor 6 (ATF6), has shown promising pharmacological effects in several disease models. Thus, it seems feasible to protect the neurons after spinal cord injury by modulating UPR. In this study, primary neurons were isolated from E17-19 C57BL/6J mouse embryos and we observed that AA147 effectively promoted the survival of neurons and alleviated neuronal apoptosis after oxygen-glucose deprivation/reoxygenation (OGD/R) invitro. This was evident through a decrease in the proportion of PI-positive and TUNEL-positive cells, an increase in BCL-2 expression, and a decrease in the expression of BAX and C-caspase3. In in-vivo experiments, these findings were corroborated by TUNEL staining and immunohistochemistry. It was also found that AA147 enhanced three arms of the unfolded protein response with reduced CHOP expression. Besides, AA147 mitigated the accumulation of ROS in neurons probably by upregulating catalase expression. Furthermore, spinal cord injury models of C57BL/6J mice were established and behavioral experiments revealed that AA147 facilitated the recovery of motor function following SCI. Thus, pharmacologic activation of ATF6 represents a promise therapeutic approach to ameliorate the prognosis of SCI.

Evaluating the Efficacy of Gross-Motor-Based Interventions for Children with Developmental Coordination Disorder: A Systematic Review.

Objectives: This review quantitatively evaluates the effectiveness of gross-motor-based interventions in children with developmental coordination disorder (DCD), examining treatment aspects such as group interventions, therapy duration, and frequency. Methods: A systematic literature review, spanning January 2010 to December 2022, identified 11 relevant articles involving 492 children. Results: Positive outcomes were observed, with a moderate to large overall effect size (Cohen's d) indicating significant improvements in motor function through strategies emphasizing activity, bodily function, games, and small group events. Notably, interventions targeting complex motor skills were crucial for enhancing preparedness and activity engagement, improving fitness, and preventing obesity in children with DCD. Conclusions: The review underscores the effectiveness of activity-oriented and body-function-focused therapies in enhancing motor skills and functioning, emphasizing the need for interventions aligned with real-world activities. Future research should explore the long-term effects and retention of motor improvements, offering valuable insights for designing targeted interventions to promote overall well-being in children with DCD.

Effects of exercise intervention on balance function in children with cerebral palsy: a systematic review and meta-analysis of randomized controlled trials

ObjectiveTo determine the effectiveness of exercise intervention on postural balance, gait parameters, and muscle strength in children with cerebral palsy by quantifying the information from randomized controlled trials (RCTs).MethodsWe conducted a systematical search for RCTs from the databases, including PubMed, ISI Web of Science, and Scopus using a between-group design involving children with cerebral palsy and assessing the effect of exercise intervention on postural balance, gait parameters, and muscle strength. The specified inclusion criteria were determined by the PICOS tool. The outcomes of included studies were evaluated by meta-analysis, and subgroup and sensitivity analyses were conducted to analyze the observed heterogeneities using Review Manager 5.4 and Stata version 18.0. The revised Cochrane risk of bias tool for randomized trials (RoB 2) was used to evaluate the risk of bias and quality of the included studies.ResultsTwenty-four studies were included in this meta-analysis, with 579 children with cerebral palsy. Exercise intervention showed a statistically significant favorable effect on gross motor function (SMD = 0.32; 95%CI [0.03 to 0.61]; I2 = 16%), anteroposterior stability index (SMD = -0.93; 95%CI [-1.69 to -0.18]; I2 = 80%), and mediolateral stability index (SMD = -0.60; 95%CI [-1.16 to -0.03]; I2 = 73%) compared to control group among children with cerebral palsy. None of the above meta-analyses exhibited publication bias, as indicated by Egger’s test with p-values greater than 0.05 for all.ConclusionsExercise is effective in improving gross motor function and balance in children with cerebral palsy. Due to the lack of studies examining the efficacy of each exercise type, we are unable to provide definitive training recommendations.

Effectiveness of Virtual Reality in Occupational Therapy for Post-Stroke Adults: A Systematic Review.

Background: In recent years, there has been a growing use of technological advancements to enhance the rehabilitation of individuals who have suffered from cerebrovascular accidents. Virtual reality rehabilitation programs enable patients to engage in a customized therapy program while interacting with a computer-generated environment. Therefore, our goal was to investigate the effectiveness of virtual reality in occupational therapy for people's rehabilitation after a cerebrovascular accident. Methods: We systematically searched databases (Pubmed/Medline, Scopus, Web of Science, and Science Direct) for randomized controlled trials published within the last 10 years. Studies involving adult stroke survivors undergoing virtual reality-based interventions aimed at improving upper-extremity motor function were included. The quality assessment followed PRISMA guidelines, with the risk of bias assessed using the Cochrane tool (version 6.4) and methodological quality evaluated using GRADEpro. Results: We selected sixteen studies that met the main criteria for the implementation of virtual reality technology. The interventions described in the articles focused mainly on the upper extremities and their fine motor skills. Conclusions: When used in conventional treatments to improve people's motor and cognitive functions after a cerebrovascular accident, virtual reality emerges as a beneficial tool. Additionally, virtual reality encourages adherence to the interventional process of rehabilitation through occupational therapy.

Bulbar muscle impairment in patients with late onset Pompe disease: Insight from the French Pompe registry.

Late onset Pompe disease (LOPD) is a rare neuromuscular disorder caused by a deficit in acid alpha-glucosidase. Macroglossia and swallowing disorders have already been reported, but no study has focused yet on its frequency and functional impact on patients' daily life. We reviewed 100 adult LOPD patients followed in 17 hospitals in France included in the French national Pompe disease registry. The Swallowing Quality of Life Questionnaire and the Sydney Swallow Questionnaire were completed by patients, and a specialist carried out a medical examination focused on swallowing and assigned a Salassa score to each patient. Respiratory and motor functions were also recorded. Subgroup analysis compared patients with and without swallowing difficulties based on Salassa score. Thirty-two percent of patients presented with swallowing difficulties, often mild but sometimes severe enough to require percutaneous endoscopic gastrostomy (1%). Daily dysphagia was reported for 20% of our patients and aspirations for 18%; 9.5% were unable to eat away from home. Macroglossia was described in 18% of our patients, and 11% had lingual atrophy. Only 15% of patients presenting with swallowing disorders were followed by a speech therapist. Swallowing difficulties were significantly associated with macroglossia (p = 0.015), longer duration of illness (p = 0.032), and a lower body mass index (p = 0.047). Swallowing difficulties in LOPD are common and have significant functional impact. Increased awareness by physicians of these symptoms with systematic examination of the tongue and questions about swallowing can lead to appropriate multidisciplinary care with a speech therapist and dietitian if needed.

Repair of spinal cord injury by bone marrow mesenchymal stem cell-derived exosomes: a systematic review and meta-analysis based on rat models

ObjectiveThis study aims to systematically evaluate the efficacy of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exo) in improving spinal cord injury (SCI) to mitigate the risk of translational discrepancies from animal experiments to clinical applications.MethodsWe conducted a comprehensive literature search up to March 2024 using PubMed, Embase, Web of Science, and Scopus databases. Two researchers independently screened the literature, extracted data, and assessed the quality of the studies. Data analysis was performed using STATA16 software.ResultsA total of 30 studies were included. The results indicated that BMSCs-Exo significantly improved the BBB score in SCI rats (WMD = 3.47, 95% CI [3.31, 3.63]), inhibited the expression of the pro-inflammatory cytokine TNF-α (SMD = -3.12, 95% CI [−3.57, −2.67]), and promoted the expression of anti-inflammatory cytokines IL-10 (SMD = 2.76, 95% CI [1.88, 3.63]) and TGF-β (SMD = 3.89, 95% CI [3.02, 4.76]). Additionally, BMSCs-Exo significantly reduced apoptosis levels (SMD = −4.52, 95% CI [−5.14, −3.89]), promoted the expression of axonal regeneration markers NeuN cells/field (SMD = 3.54, 95% CI [2.65, 4.42]), NF200 (SMD = 4.88, 95% CI [3.70, 6.05]), and the number of Nissl bodies (SMD = 1.89, 95% CI [1.13, 2.65]), and decreased the expression of astrogliosis marker GFAP (SMD = −5.15, 95% CI [−6.47, −3.82]). The heterogeneity among studies was primarily due to variations in BMSCs-Exo transplantation doses, with efficacy increasing with higher doses.ConclusionBMSCs-Exo significantly improved motor function in SCI rats by modulating inflammatory responses, reducing apoptosis, inhibiting astrogliosis, and promoting axonal regeneration. However, the presence of selection, performance, and detection biases in current animal experiments may undermine the quality of evidence in this study.

Enriched music-supported therapy for individuals with chronic stroke: a randomized controlled trial.

Many stroke survivors still present with upper-limb paresis six months post-stroke, impacting their autonomy and quality of life (QoL). We designed an enriched Music-supported Therapy (eMST) program to reduce disability in this population. We evaluated the eMST's effectiveness in improving functional abilities and QoL in chronic stroke individuals compared to the conventional motor program Graded Repetitive Arm Supplementary Program (GRASP). We conducted a pragmatic two-arm parallel-group randomized controlled trial with a 3-month follow-up and masked assessment. The eMST involved playing instruments during individual self-administered and group music therapy sessions. The GRASP consisted of self-administered motor exercises using daily objects. Both interventions were completed at home with telemonitoring and involved four one-hour weekly sessions for 10weeks. The primary outcome was upper-limb motor function measured with the Action Research Arm Test. Secondary outcomes included motor impairment, daily life motor performance, cognitive functions, emotional well-being, QoL, self-regulation, and self-efficacy. Intention-to-treat (ITT)and per-protocol(PP) analyses were conducted including participants who discontinued the intervention and those who completed it entirely, respectively. Fifty-eight chronic stroke patients were randomized to the eMST-group (n = 26; age: 64.2 ± 12.5; 6[23.1%] females; 2.8 ± 2.9years post-stroke), and the control group (n = 32; age: 62.2 ± 12; 8[25%] females; 1.8 ± 6.2years post-stroke). The eMST-group had more participants achieving a clinically relevant improvement in motor impairment post-intervention than the control group for the ITT (55% vs 21.6%; OR = 4.5 (95% CI 1.4-14); p = .019) and PP analyses (60% vs 20%; OR = 6 (95% CI 1.5-24.7); p = .024), sustained at follow-up. The eMST-group reported greater improvements in emotion (difference = 11.1 (95% CI 0.8-21.5; p = 0.36) and participation (difference = 10.3 (95% CI 0.6-25.9); p = 0.41) subscales of QoL, and higher enjoyment during the sessions (difference = 1 (95% CI 0.3-1.5); p = 0.12). No changes were found in other outcomes. eMST demonstrated superiority over conventional motor rehabilitation program in enhancing upper-limb functions and QoL in chronic stroke individuals. ClinicalTrials.gov (ID: NCT04507542).

Implicit learning provides advantage over explicit learning for gait-cognitive dual-task interference

Dual-task performance holds significant relevance in real-world scenarios. Implicit learning is a possible approach for improving dual-task performance. Analogy learning, utilizing a single metaphor to convey essential information about motor skills, has emerged as a practical method for fostering implicit learning. However, evidence supporting the effect of implicit learning on gait-cognitive dual-task performance is insufficient. This exploratory study aimed to examine the effects of implicit and explicit learning on dual-task performance in both gait and cognitive tasks. Tandem gait was employed on a treadmill to assess motor function, whereas serial seven subtraction tasks were used to gauge cognitive performance. Thirty healthy community-dwelling older individuals were randomly assigned to implicit or explicit learning groups. Each group learned the tandem gait task according to their individual learning styles. The implicit learning group showed a significant improvement in gait performance under the dual-task condition compared with the explicit learning group. Furthermore, the implicit learning group exhibited improved dual-task interference for both tasks. Our findings suggest that implicit learning may offer greater advantages than explicit learning in acquiring autonomous motor skills. Future research is needed to uncover the mechanisms underlying implicit learning and to harness its potential for gait-cognitive dual-task performance in clinical settings.

Wearable-Based Kinematic Analysis of Upper-Limb Movements During Daily Activities Could Provide Insights into Stroke Survivors' Motor Ability.

Frequent and objective monitoring of motor recovery progression holds significant importance in stroke rehabilitation. Despite extensive studies on wearable solutions in this context, the focus has been predominantly on evaluating limb activity. This study aims to address this limitation by delving into a novel measure of wrist kinematics more intricately related to patients' motor capacity. To explore a new wearable-based approach for objectively and reliably assessing upper-limb motor ability in stroke survivors using a single inertial sensor placed on the stroke-affected wrist. Seventeen stroke survivors performed a series of daily activities within a simulated home setting while wearing a six-axis inertial measurement unit on the wrist affected by stroke. Inertial data during point-to-point upper-limb movements were decomposed into movement segments, from which various kinematic variables were derived. A data-driven approach was then employed to identify a kinematic variable demonstrating robust internal reliability, construct validity, and convergent validity. We have identified a key kinematic variable, namely the 90th percentile of movement segment distance during point-to-point movements. This variable exhibited robust reliability (intra-class correlation coefficient of .93) and strong correlations with established clinical measures of motor capacity (Pearson's correlation coefficients of .81 with the Fugl-Meyer Assessment for Upper-Extremity; .77 with the Functional Ability component of the Wolf Motor Function Test; and -.68 with the Performance Time component of the Wolf Motor Function Test). The findings underscore the potential for continuous, objective, and convenient monitoring of stroke survivors' motor progression throughout rehabilitation.

Evaluation of the effects of a gamified, fully immersive and stroke-specific virtual reality intervention for improving disability and quality of life in patients with stroke in the subacute phase: study protocol of the RESET randomised trial

Stroke is the leading cause of disability and the second cause of death worldwide. The increasing burden of stroke underscores the importance of optimising rehabilitation protocols. Virtual reality (VR) can...

Nusinersen Improves Motor Function in Type 2 and 3 Spinal Muscular Atrophy Patients across Time.

Spinal muscular atrophy (SMA) is a genetic disorder primarily caused by mutations in the SMN1 gene, leading to motor neuron degeneration and muscle atrophy, affecting multiple organ systems. Nusinersen treatment targets gene expression and is expected to enhance the motor function of voluntary muscles in the limbs and trunk. Motor skills can be assessed through specific scales like the Revised Upper Limb Module Scale (RULM) and Hammersmith Functional Motor Scale Expanded (HFMSE). This study aims to evaluate the influence of nusinersen on the motor skills of patients with SMA Type 2 and 3 using real-world data collected over 54 months. A prospective longitudinal study was conducted on 37 SMA patients treated with nusinersen, analyzing data with R statistical software. The outcomes revealed significant improvements in motor functions, particularly in SMA Type 3 patients with higher RULM and HFSME scores. Additionally, GEE analysis identified time, type, age, and exon deletions as essential predictors of motor score improvements. The extended observation period is both a major strength and a limitation of this research, as the dropout rates could present challenges in interpretation. Variability in responses, influenced by genetic background, SMA type, and onset age, highlights the need for personalized treatment approaches.

Circadian Interventions in Preclinical Models of Huntington's Disease: A Narrative Review.

Huntington's Disease (HD) is a neurodegenerative disorder caused by an autosomal-dominant mutation in the huntingtin gene, which manifests with a triad of motor, cognitive and psychiatric declines. Individuals with HD often present with disturbed sleep/wake cycles, but it is still debated whether altered circadian rhythms are intrinsic to its aetiopathology or a consequence. Conversely, it is well established that sleep/wake disturbances, perhaps acting in concert with other pathophysiological mechanisms, worsen the impact of the disease on cognitive and motor functions and are a burden to the patients and their caretakers. Currently, there is no cure to stop the progression of HD, however, preclinical research is providing cementing evidence that restoring the fluctuation of the circadian rhythms can assist in delaying the onset and slowing progression of HD. Here we highlight the application of circadian-based interventions in preclinical models and provide insights into their potential translation in clinical practice. Interventions aimed at improving sleep/wake cycles' synchronization have shown to improve motor and cognitive deficits in HD models. Therefore, a strong support for their suitability to ameliorate HD symptoms in humans emerges from the literature, albeit with gaps in our knowledge on the underlying mechanisms and possible risks associated with their implementation.

Efficacy and threshold dose of intensive training targeting mobility for children with cerebral palsy: A systematic review and meta-analysis.

To systematically review the evidence for intensive mobility training in cerebral palsy (CP) and to determine the minimum effective dose to improve mobility. Randomized controlled trials (RCTs) or quasi-RCTs that included participants with CP, and which used intensive task-oriented training (TOT) mobility interventions and reported mobility outcomes, were included. Five databases were searched; two independent reviewers selected studies and extracted data. The Grading of Recommendations Assessment, Development, and Evaluation system and the Cochrane Risk of Bias 2 tool were used to rate the certainty of evidence at the outcomes level and to determine the risk of bias respectively. Meta-analyses were conducted with clinically homogeneous studies. Threshold dose was analysed through meta-regression. Forty-six RCTs with 1449 participants (mean age range 1 year 2 months to 16 years 4 months) were included. TOT had statistically and clinically significant effects on walking speed (p = 0.001), cadence (p = 0.02), gross motor function (p = 0.03), and functional mobility (p = 0.009) compared with control interventions. The threshold dose was undeterminable owing to the high heterogeneity of studies. TOT may improve walking speed, walking endurance, and balance. Studies with homogeneous samples and outcomes are needed to support clinical recommendations for intensive mobility interventions.

Customized Flexible Osteoid Electrode for Traumatic Brain Injury Induced Posttraumatic Epilepsy Monitoring

AbstractTraumatic brain injury (TBI)‐induced post‐traumatic epilepsy (PTE) is a serious brain disease that causes the loss of motor functions, cognitive impairments, and even death. Real‐time and long‐term electrophysiological signal monitoring has significant implication for the treatment of patient with TBI. Brain–computer interfaces (BCIs) utilizing flexible electrodes enable accurate epilepsy identification by electrocorticography (ECoG) signal monitoring. In this study, a customized flexible osteoid electrode is developed, which contributes to demands and personal differentiation among patients with TBI. The end product of osteoid electrode after full osseointegration will be a stable and firmly integrated structure within the bone tissue, providing a secure platform for continuous electrophysiological signal monitoring. The flexibility and conductivity of the osteoid electrode enables high‐quality and long‐term epilepsy monitoring. Biocompatibility of the osteoid electrode is also demonstrated by in vitro cell experiments. Simultaneously, the porous osteoid electrode also exhibits osseointegration ability based on potential long‐term ECoG signal monitoring, which suggests its potential for the comprehensive treatment of TBI patients. This work not only introduces a potential therapeutic scaffold for TBI‐related diseases, but also provides promising techniques for clinical ECoG monitoring in patients with TBI.

Ex Vivo Study of Colon Health, Contractility and Innervation in Male and Female Rats after Regular Exposure to Instant Cascara Beverage.

Instant Cascara (IC) is a sustainable beverage made from dried coffee cherry pulp, a by-product of coffee processing. It is rich in nutrients and bioactive compounds and has a high concentration of antioxidants. This study explored the impact of regular IC consumption on colonic motor function and innervation. Over a period of 4 weeks, male and female healthy rats were given drinking water containing 10 mg/mL of IC. Thereafter, colon samples were obtained to evaluate the longitudinal (LM) and circular (CM) smooth muscle contractile response to acetylcholine (ACh) and electrical field stimulation (EFS) in an organ bath, before and after atropine administration (10-6 M). Histological and immunohistochemical analyses assessed colon damage, muscle thickness, and immunoreactivity to substance P (SP) and neuronal nitric oxide synthase (nNOS). ACh and EFS induced similar responses across groups, but the CM response to EFS was greater in females compared with males, despite their lower body weight. Atropine completely blocked the response to ACh but only partially antagonized the neural response to EFS, particularly that of CM in females treated with IC, which had a greater liquid intake than those exposed to water. However, in the myenteric ganglia, no statistically significant differences were observed in SP or nNOS. Our results suggest that regular IC exposure may enhance specific neural pathway functions, particularly in females, possibly due to their increased IC consumption.

Combination AAV therapy with galectin-1 and SOD1 downregulation demonstrates superior therapeutic effect in a severe ALS mouse model

Neuroinflammation is a miscreant in accelerating progression of many neurodegenerative diseases, including ALS. However, treatments targeting neuroinflammation alone have led to disappointing results in clinical trials. Both neuronal and non-neuronal cell types have been implicated in pathogenesis of ALS, and multiple studies have shown correction of each cell type has beneficial effect on disease outcome. Previously, we showed that AAV9-mediated SOD1 suppression in motor neurons and astrocytes significantly improves motor function and extends survival in ALS mouse models. Despite neuron and astrocyte correction, ALS mice still succumb to death with microgliosis observed in endpoint tissue. Therefore, we hypothesized that the optimal therapeutic approach will target and simultaneously correct motor neurons, astrocytes, and microglia. Here, we developed a novel approach to indirectly target microglia with Galectin-1 and combined this with our previously established AAV9.SOD1.shRNA treatment. We show Galectin-1 conditioning of SOD1G93A microglia reduces inflammatory markers and rescues motor neuron death in vitro. When paired with SOD1 downregulation, we found a synergistic effect of combination treatment in vivo and show a significant extension of survival of SOD1G93A mice over SOD1 suppression alone. These results highlight the importance of targeting inflammatory microglia as a critical component in future therapeutic development.

Utilizing Entropy of Cadence to Optimize Cycling Rehabilitation in Individuals With Parkinson's Disease.

Previous studies have established that increased Sample Entropy (SampEn) of cadence, a measure of non-linear variability, during dynamic cycling leads to greater improvements in motor function for individuals with Parkinson's disease (PD). However, there is significant variability in responses among individuals with PD due to symptoms and disease progression. The aim of this study was to develop and test a paradigm for adapting a cycling exercise intervention using SampEn of cadence and rider effort to improve motor function. Twenty-two participants were randomized into either patient-specific adaptive dynamic cycling (PSADC) or non-adaptive (NA) group. SampEn of cadence was calculated after each of the 12 sessions, and motor function was evaluated using the Kinesia test. Pearson's correlation coefficient was used to analyze the relationship between SampEn of cadence and motor function improvement. Multiple linear regression (MLR) was used to identify the strongest predictors of motor function improvement. Pearson's correlation coefficient revealed a significant correlation between SampEn of cadence and motor function improvements (R2 = -.545, P = .009), suggesting that higher SampEn of cadence led to greater motor function improvement. MLR demonstrated that SampEn of cadence was the strongest predictor of motor function improvement (β = -8.923, t = -2.632, P = .018) over the BMI, Levodopa equivalent daily dose, and effort. The findings show that PSADC paradigm promoted a greater improvement in motor function than NA dynamic cycling. These data will be used to develop a predictive model to optimize motor function improvement after cycling in individuals with PD.